A model system is presented for investigating the regulation of gene expression in Drosophila. The objective of the proposed research is to provide a genetic and biochemical analysis of the relationship of the maroon-like, low xanthine dehydrogenase and cinnamon loci to the final expression of three enzymes, xanthine dehydrogenase, aldehyde oxidase and pyridoxal oxidase. These three enzymes, physically separable, do not share major structural subunits, are not interdependent with respect to their individual activities and are encoded by separate structural genes. Genetic and biochemical evidence argues that although maroon-like, cinnamon and low xanthine dehydrogenase are each deficient for all three enzymatic activities, they do not provide major structural elements to the enzymes. Recent biochemical evidence argues that this group of Drosophila loci is analogous to the cnx loci of Aspergillus which control the synthesis and/or utilization of a molybdenum cofactor commonly required by molybdenum bearing enzymes. Biochemical studies of the relationship of the maroon-like, cinnamon and low xanthine dehydrogenase functions with respect to the cofactor and to the three enzymatic activities will be accomplished by the use of a sensitive bioassay for the cofactor and/or the use of 99Mo, a rather specific probe since it appears only in the cofactor and in the few molybdo-proteins found in Drosophila. In Drosophila, the selection of an array of new mutants as well as fine structural analysis will be carried out through the use of a nutritional selective system applicable to all xanthine dehydrogenase-negative loci.